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. 2018 Mar 28;12:88. doi: 10.3389/fncel.2018.00088

Figure 1.

Figure 1

Physical exercise ameliorates hypothalamic insulin and leptin signaling, and consequently improves diet control and WAT browning and stimulates thermogenesis. Physical exercise improves leptin signaling in POMC neurons by increasing JAK2 and STAT3 tyrosine phosphorylation, which in turn migrates to the nucleus and transcribes anorexigenic neuropeptides. Furthermore, physical exercise enhances IRS-1/2 and Akt activation, which in turn improves Fox01 phosphorylation, allowing this protein to translocate out of the nucleus and stop transcribing orexigenic neuropeptides. Finally, proteins that inhibit insulin and leptin pathways, such as JNK, IKKβ, and PTP1B, have their activity decreased by physical exercise. Once insulin and leptin signaling has been restored in POMC neurons, the WAT browning process is increased via the sympathetic nervous system, and the signal propagation from an adipocyte receiving a sympathetic signal from a cluster of adipocytes in close proximity is connexin 43 (Cx43)-dependent. On the other hand, stimulation of AgRP neurons suppresses WAT browning. Akt, Protein kinase B; ER, Endoplasmic reticulum; FOX01, Forkhead box protein 01; IKKβ, Inhibitor of nuclear factor kappa-B kinase beta; IL-6, Interleukin 6; IR, Insulin receptor; IRS-1/2, Insulin Receptor Substrate 1 and 2; JAK2, Janus kinase 2; JNK, C-Jun-N terminal kinase; POMC, Pro-opiomelanocortin; PTP1B, Protein tyrosine phosphatase 1B; STAT3, Signal transducer and activator of transcription 3; WAT, White Adipose Tissue.